Computational Biology

Theoretical methods and mathematical modeling can be applied to investigate complex physical systems that are found in biological organisms. Computer simulations are a common tool to analyze the interactions of biological structures at the molecular level, or the connections among different subsystems in large-scale networks, which are crucial to understand the basic mechanisms in the proteomics and metabolomics fields

Ligand binding. Receptor-ligand interactions are responsible of molecular recognition, binding, transport and release. These mechanisms are fundamental in many processes that are vital in any living organism, and can be exploited in several applications of nanotechnology. Molecular dynamics simulations and docking calculations are theoretical tools that allow us to determine a model of interaction between a receptor and a variety of ligands. These computational techniques are useful to predict structural and dynamic properties that determine the functionality of a molecular complex between transport proteins and small compounds, such as ligands of pharmaceutical interest.

Protein folding. Proteins are molecular ‘nanomachines’ that acquire their tridimensional structure through a spontaneous process of folding. This phenomenon is central for some of the basic mechanisms of life. Furthermore, their competitive processes (unfolding and misfolding) lead to a loss of function and are correlated to some serious pathologies. Protein folding is an intrinsically complex molecular process that needs to be investigated with a combined theoretical and experimental approach. Molecular dynamics simulations and other computational methods are able to reveal crucial details of the folding reaction.

Regulatory RNA. Overcoming the decades’ old view according to which they are mere intermediates between DNA and proteins in the central dogma of molecular biology, RNAs are increasingly recognized for the remarkable variety of functional roles they play in eukaryotic gene expression. Non-coding RNAs (ncRNAs), in particular, are deeply involved in developmental programs and disease, to the point of having become targets of novel therapeutic approaches that aim at either inhibiting or enhancing their functionality. Importantly, most ncRNAs act by protein-mediated binding to other nucleic acids, leading to complex inter-dependencies be- tween coding and ncRNAs, RNA-binding proteins and DNA. Their central role in regulation is perhaps best exemplified by microRNAs (miRNAs), small ncRNAs of 20–25 nucleotides (nt) that mediate post-transcriptional regulation (PTR) via gene expression silencing in animals. miRNAs are believed to affect the expression of about two-thirds of protein-coding genes in humans. Their apparent ubiquity, together with the strong topological heterogeneities that characterize the PTR network that maps out the known interactions between miRNAs and other RNA species (such as mRNAs), has lead to the idea that competition for shared miRNAs can cause an effective positive interaction between different transcripts, currently referred to as the ‘ceRNA effect’. In this context, we are interested in quantifying the role and effectiveness of miRNA-mediated RNA cross-talk, with the goal of clarifying (i) under which conditions it outperforms other regulatory mechanisms, for instance in processing gene expression noise; (b) whether it can carry a significant systemic role; and (c) its relevance in specific biological cases of differentiation and disease.

Cell growth and its biosynthetic costs. The coupling between the physiology of cell growth and cellular composition has been actively investigated since the 1940s. In exponentially growing bacteria, such interdependence is best expressed in a quantitative way by the bacterial ‘growth laws’ that directly relate the protein, DNA and RNA content of a cell to the growth rate. Many such laws have been experimentally characterized and many more are currently being probed at increasingly high resolution. The emerging scenario suggests that proteome organization in bacteria is actively regulated in response to the growth conditions. Several phenomenological models explain the origin of different growth laws at coarse-grained levels. By contrast, genome-scale approaches probing such relationships at the molecular level are far less developed. We have developed a mathematical modeling scheme called Constrained Allocation Flux Balance Analysis or CAFBA, in which the costs of gene expression are accounted for effectively through a single global constraint on metabolic fluxes, encodeing for the relative adjustment of proteome sectors at different growth rates. Using bacteria as the initial model organisms, we are interested in quantifying the trade-off between cell growth and its associated biosynthetic costs, generating testable predictions about the way in which the usage of metabolic pathways and protein expression levels are modulated by the growth conditions.

Cell-to-cell variability in exponentially growing bacteria. Current experimental techniques (see e.g. the ‘mother machine’) can probe physiological variability by characterizing e.g. growth rate distributions for bacterial populations at single cell resolution. These distributions reflect noise at various levels, from intracellular stochasticity in gene expression and metabolite levels to fluctuations in the extracellular medium. However, upon controlling the latter, they provide a window to analyze the role of noise in the genotype-phenotype relationship. Straightforward sam- pling of the feasible space predicted by mathematical models, however, does not explain the observed statistics. We are therefore interested in identifying a physical or biological principle that drives the selection of observed growth states and hence shed light on the origin of the observed phenotypic diversity.

Latest News

The IV edition of TERAMETANANO, the International Conference on Terahertz Emission, Metamaterials and Nanophotonics, will take place in Lecce (Italy) from 27 to 31 of May 2019 in the 16th-century Castle of Charles V with two special nights that will be held in an original Theatre of Roman period.

TERAMETANANO is an annual conference that gather physicists studying a wide variety of phenomena in the areas of nano-structures, nano-photonics and meta-materials, with special attention to the coupling between light and matter and in a broad range of wavelengths, going from the visible up to the terahertz.

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